H2O2-Depleting and O2-Generating Selenium Nanoparticles for Fluorescence Imaging and Photodynamic Treatment of Proinflammatory-Activated Macrophages

Kun-Ying Lu; Po-Yen Lin; Er-Yuan Chuang; Chwen-Ming Shih; Tsai-Mu Cheng; Tsung-Yao Lin; Hsing-Wen Sung; Fwu-Long Mi

doi:10.1021/acsami.6b15515

H₂O₂-Depleting and O₂-Generating Selenium Nanoparticles for Fluorescence Imaging and Photodynamic Treatment of Proinflammatory-Activated Macrophages

ACS Appl Mater Interfaces. 2017 Feb 15;9(6):5158-5172. doi: 10.1021/acsami.6b15515. Epub 2017 Feb 1.

Authors

Kun-Ying Lu¹, Po-Yen Lin², Er-Yuan Chuang³, Chwen-Ming Shih^{1

4}, Tsai-Mu Cheng⁵, Tsung-Yao Lin¹, Hsing-Wen Sung^{2

6}, Fwu-Long Mi^{1

4

7}

Affiliations

¹ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University , Taipei 11031, Taiwan.
² Department of Chemical Engineering, National Tsing Hua University , Hsinchu 30013, Taiwan.
³ Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University , Taipei 11031, Taiwan.
⁴ Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University , Taipei 11031, Taiwan.
⁵ Graduate Institute of Translational Medicine, College of Medicine and Technology, Taipei Medical University , Taipei 11031, Taiwan.
⁶ Institute of Biomedical Engineering, National Tsing Hua University , Hsinchu 30013, Taiwan, ROC.
⁷ Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University , Taipei 11031, Taiwan.

PMID: 28120612
DOI: 10.1021/acsami.6b15515

Abstract

Macrophages have a pivotal role in chronic inflammatory diseases (CIDs), so imaging and controlling activated macrophage is critical for detecting and reducing chronic inflammation. In this study, photodynamic selenium nanoparticles (SeNPs) with photosensitive and macrophage-targeting bilayers were developed. The first layer of the photosensitive macromolecule was composed of a conjugate of a photosensitizer (rose bengal, RB) and a thiolated chitosan (chitosan-glutathione), resulting in a plasmonic coupling-induced red shift and broadening of RB absorption bands with increased absorption intensity. Electron paramagnetic resonance (EPR) and diphenylanthracene (DPA) quenching studies revealed that the SeNPs that were coated with the photosensitive layer were more effective than RB alone in producing singlet oxygen (¹O₂) under photoirradiation. The second layer of the activated macrophage-targetable macromolecule was synthesized by conjugation of hyaluronic acid with folic acid using an ethylenediamine linker. Proinflammatory-activated macrophages rapidly internalized the SeNPs that were covered with the targeting ligand, exhibiting a much stronger fluorescence signal of the SeNPs than did the nonactivated macrophages. Since proinflammatory-activated macrophage was known to generate a substantial amount of H₂O₂ while the inflamed site generally caused inflammation-associated tissue hypoxia, the SeNPs were further modified with O₂ self-sufficient function for photodynamic therapy. Catalase was immobilized on the SeNPs by the formation of disulfide bonds. Intracellular reduction of disulfide bonds induced the subsequent release of catalase, which catalyzed the decomposition of H₂O₂. The H₂O₂-depleting and O₂-generating photodynamic SeNPs efficiently killed activated macrophages and quenched the intracellular H₂O₂ and NO that are associated with inflammation. The SeNPs may have potential as a theranostic nanomaterial to image and control the activation of macrophages.

Keywords: Se nanoparticles; fluorescence imaging; macrophage; photodynamics.

MeSH terms

Fluorescence
Hydrogen Peroxide
Macrophages
Nanoparticles*
Oxygen
Selenium

Substances

Hydrogen Peroxide
Selenium
Oxygen